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Ann Thorac Surg 1997;64:1790-1794
© 1997 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Release of Proinflammatory Cytokines During Pediatric Cardiopulmonary Bypass: Heparin-Bonded Versus Nonbonded Oxygenators

Cardiothoracic Surgery Department, Killingbeck Hospital, Leeds, United Kingdom

Accepted for publication June 23, 1997.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.

Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.

Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).

Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The interaction of blood with nonphysiologic surfaces during cardiopulmonary bypass (CPB) activates numerous biologic pathways, including the complement, coagulation, fibrinolytic, and kallikrein cascades, resulting in a systemic inflammatory syndrome [1]. Recent studies also have revealed elevated levels of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) after CPB [2–4], and these may contribute to postbypass cardiac dysfunction [5, 6]. If pathways activation and cytokine release could be reduced during CPB, some of the adverse clinical sequelae of CPB might be avoided. A number of approaches [7–10], including improvement of biocompatibility by heparin surface-bonding of CPB circuits, have been suggested. Several clinical studies have demonstrated that fully heparin-bonded bypass circuits reduce neutrophil and complement activation, with improved clinical outcome [10, 11] and reduced cytokine release [12]. These studies were carried out in adult cohorts, however, and complications of CPB (particularly generalized capillary leak syndrome) are more prominent in children.

Factors limiting the use of heparin-bonded CPB circuits in routine adult and pediatric cardiac operations include cost, because it is still uncertain whether the routine use of these expensive circuits is justified. Convenience also is a problem because each cardiac unit has its own CPB circuit design, with custom-built circuits undergoing heparin bonding. To overcome these difficulties, we hypothesized that the use of heparin-bonded oxygenators (which comprise more than 80% of the circuit surface area) [13] with otherwise nonbonded circuits might be an attractive alternative that could reduce the proinflammatory response to CPB and improve postoperative recovery. Complement and leukocyte activation and cytokine release were measured during and after pediatric CPB.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
After ethical committee approval and informed consent was obtained, 21 consecutive pediatric patients undergoing hypothermic (28°C) CPB procedures for the repair of congenital heart disease were assigned randomly to undergo operation using either a heparin-bonded oxygenator (Carmeda; Minimax Medtronic Inc, Minneapolis, MN) (group H, n = 11) or a matched nonbonded oxygenator (Minimax Medtronic Inc) (group C, n = 10). The operative procedures performed are outlined in Table 1. All patients received a similar balanced anesthetic, including nitrous oxide, a volatile agent, a neuromuscular blocking agent, and opiate analgesia. Heparin (300 IU/kg) was given before aortic cannulation and activated clotting time was maintained above 450 seconds throughout the procedure. Heparin requirements during CPB were not different between the two groups.

Sample Collection
Blood samples were drawn from the central venous line or, during CPB, from an arterial port of the oxygenator at the following times: (1) immediately after the induction of anesthesia, (2) 5 minutes after the onset of CPB, (3) at the end of CPB, (4) 30 minutes after protamine neutralization, (5) 2 hours after operation, and (6) 24 hours after operation. Blood was drawn into ethylenediaminetetraacetic acid tubes for assessment of hematocrit value, platelet count, and leukocyte count, and into sodium citrate solution (3.2% wt/vol in a 9:1 ratio) for all other measurements. The citrated blood was centrifuged at 3,000 rpm for 10 minutes at 4°C, and the plasma immediately was separated, aliquoted, and frozen at -80°C.

Assay Techniques: Cytokines, Terminal Complement Complex, and Plasma Neutrophil Elastase Measurements
Enzyme-linked immunoassays for tumor necrosis factor- (TNF-), IL-6, and IL-8 were performed using commercially available kits (R&D Systems, Minneapolis, MN) according to the manufacturer's instructions. In brief, samples were diluted 1:1 in appropriate diluent and incubated for 2 hours at room temperature in wells coated with monoclonal anticytokine antibody. Wells were washed and then incubated similarly with polyclonal anticytokine antibody conjugated to horseradish peroxidase. After further washes, a substrate solution containing tetramethylbenzidine and hydrogen peroxide was added; the reaction was stopped after 20 minutes with sulfuric acid (2 mol/L), and absorbances were measured using a microplate reader set to 450 nm with wavelength correction set to 570 nm.

Plasma leukocyte elastase in complex with ₁-protease inhibitor (E. Merck, Darmstadt, Germany) was determined using an autoanalyzer technique. Terminal complement complex (C5b-9) was measured in plasma by an enzyme-linked immunosorbent assay (Quidel, San Diego, CA) [12]. The limit of sensitivity of each assay undertaken was as follows: TNF- = 4 pg/mL, IL-6 = 3 pg/mL, IL-8 = 50 pg/mL, C5b-9 = 12 ng/mL, and elastase = 20 ng/mL. The interassay coefficients of variation for batch-analyzed markers were less than 8% in each case. All samples were assayed in duplicate, and concentrations were calculated from a standard curve prepared concurrently with each assay. No adjustment was made for hemodilution for each of the measured analytes.

Clinical variables recorded to evaluate clinical outcome of the patients included 24-hour postoperative blood loss and packed red cell transfusion and time of extubation. The anesthetist and intensive care unit nurses were unaware of the type of oxygenator used, and both groups of patients were managed according to our current extubation protocols.

Statistical Analysis
Results are expressed as medians with ranges given in parentheses. The Mann-Whitney U test was used to test differences between groups at each time point and for each subject's maximum level of each marker. The Wilcoxon test was used to test intragroup differences. Spearman's rank correlation coefficient was used to assess association (Statistica software). In all cases, p values less than 0.05 were considered significant.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
The two study groups were well matched in pathology, age, sex, duration of CPB, and duration of aortic cross-clamping (p = 0.87 to 0.97, not significant). There were no deaths in either group. One patient in group H and 2 in group C were ventilated for more than 24 hours. The average total ventilatory time in group H was significantly less than in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01). There was no statistically significant difference in the postoperative blood loss over the first 24 hours (group H versus group C: 120 [range, 49 to 210] versus 140 [range, 60 to 297] mL; p = 0.12). Renal function (serum creatinine and urea levels) and inotropic agent requirements were not significantly different between the groups.

Cytokines
TUMOR NECROSIS FACTOR-
Traces of TNF- were detected in only 2 patients in group H and in no patients in group C (data not shown).

INTERLEUKIN-6
In both groups, plasma concentrations of IL-6 were increased at the end of CPB from initially undetectable levels at baseline to peak levels 2 hours after protamine administration: 200 (range, 83 to 510) pg/mL in group H versus 185 (range, 113 to 4,900) pg/mL in group C. Interleukin-6 levels fell 24 hours after operation but they remained significantly higher in group C than in group H (p < 0.05) (Fig 1).

View larger version (17K): [in this window] [in a new window]   Fig 1. . Changes in the median circulating concentration of interleukin-6 (IL-6) with time in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded (open triangles) and nonbonded (closed squares) oxygenators. Error bars relate to the 25th to 75th interquartile range. (post-p = after perfusion.)

View larger version (15K): [in this window] [in a new window]   Fig 2. . Changes in the median circulating concentration of interleukin-8 (IL-8) with time in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded (open triangles) and nonbonded (closed squares) oxygenators. Error bars relate to the 25th to 75th interquartile range. (post-p = after perfusion.)

View larger version (18K): [in this window] [in a new window]   Fig 3. . Changes in the median circulating concentration of terminal complement complex (C5b-9) with time in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded (open triangles) and nonbonded (closed squares) oxygenators. Error bars relate to the 25th to 75th interquartile range. (post-p = after perfusion.)

Plasma Leukocyte Elastase
In both groups (Fig 4), plasma leukocyte elastase levels increased significantly during CPB from preoperative values of less than 20 ng/mL. In both groups, levels peaked 30 minutes after protamine administration (341 [range, 174 to 635] ng/mL in group C versus 242 [range, 169 to 596] ng/mL in group H) before returning to preoperative levels in most of the patients. Plasma levels of elastase remained significantly higher 2 hours and 24 hours after protamine administration in group C than in group H (p < 0.02 and p < 0.01, respectively). There was no significant correlation between elastase, C5b-9, and IL-8 levels in either group.

View larger version (17K): [in this window] [in a new window]   Fig 4. . Changes in the median circulating concentration of elastase with time in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded (open triangles) and nonbonded (closed squares) oxygenators. Error bars relate to the 25th to 75th interquartile range. (post-p = after perfusion.)

	Comment

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

Tumor necrosis factor- was measured because it promotes leukocyte adhesion and causes marked activation of leukocytes, resulting in degranulation [5]. There has been inconsistent reporting of detectable levels of perioperative TNF- in adults and children [2, 4, 8, 14]. In our study, TNF- was not detected in either group. Most studies now seem to suggest that TNF- is not an important systemic mediator of the inflammatory response to CPB. Interleukin-6 is involved in the modulation of the acute-phase response and is synthesized by a variety of cell types, including endothelium and leukocytes [15]. Serum levels of IL-6 have been shown to be a marker of the severity of tissue damage, and they have been used as a prognostic index in septic shock [16]. A number of investigators have shown the beneficial effects of heparin-bonded whole CPB circuits in terms of diminished inflammatory response, measured as C5b-9 and elastase levels [10, 12], IL-6 and IL-8 release, and improved clinical outcome [9, 11]. In the present study, IL-6 levels in group C were more pronounced after CPB and remained significantly higher than in group H 24 hours after operation. This finding may have important clinical implications that warrant further study in a large group of patients, because IL-6 plays an important role in the postoperative inflammatory response.

Activation of the complement cascade during CPB takes place predominantly through the alternative pathways and results in the activation of C3, which in turn generates the formation of C5a and C5b-9 through a complex amplifying reaction. Some have suggested that postbypass morbidity is related directly to the degree of complement activation [1, 17]. In this regard, it has been recommended that the biocompatibility of extracorporeal circuits be assessed by the degree of complement activation, particularly C5b-9 [18, 19]. In our study, because only the terminal complex of complement activation was measured, the mechanism by which the lower concentration of C5b-9 in the heparin-bonded oxygenator group occurred remains to be elucidated. Studies have shown that heparin intensifies the inactivation of C3b and prevents the generation of C3 amplification convertase [20, 21]. Apart from the possible inhibitory effect of heparin on the activation of alternative pathways, the lower level of C5b-9 might be explained by its direct binding to the heparin-bonded oxygenator [22]. A number of studies have shown that an increased level of C5b-9 during CPB precedes IL-6 release [2], which is consistent with the findings of this study.

Complement activation activates neutrophils, which results in elastase release during CPB [23]. This natural serine protease, which is an important marker of neutrophil activation, increases in the plasma as elastase–₁-antiprotease complex during operation and has been implicated in CPB-related lung parenchymal and endothelial injury [14]. In the present study, postoperative plasma leukocyte elastase levels were significantly lower in group H than in group C, consistent with improved lung function. Although we observed no significant correlation between elastase and IL-8 levels, an association has been found by others [4]. Clearly, the complex interactions of these molecules and cells at the endothelial level cannot be reflected accurately in statistical correlations of plasma levels.

Inflammatory capillary leak and edema (which is pronounced in children) is understood poorly, but IL-8 may be involved in its pathogenesis [4, 12]. Interleukin-8 is produced from monocytes, fibroblasts, endothelial cells, and alveolar macrophages after lung reperfusion, and from neutrophils [24]. In contrast to other studies with full-circuit heparin bonding, differences in IL-8 release failed to achieve significance in our study [12].

Like other studies [9–12], the release of IL-6, C5b-9, and elastase in our study was significantly less in the heparin-bonded group than in the control group, but this difference failed to achieve significance in terms of IL-8 release. This finding may be due to (1) the small number of patients, (2) the different type of patients used (pediatric rather than adult), or (3) the fact that fully heparin-bonded circuits may be superior to heparin-bonded oxygenators only in terms of their suppression of IL-8. It also could be argued that one might not expect a difference because ischemia-reperfusion, which may be the main stimulus for IL-8 release, occurs equally in both groups.

In general, proinflammatory markers (IL-6, plasma leukocyte elastase, and C5b-9) were significantly lower in group H; therefore, this study demonstrated that significant biocompatibility of the extracorporeal circulation, particularly in pediatric patients (in whom inflammatory capillary leak and edema is more pronounced than in adults), can be achieved with the isolated use of a heparin-bonded oxygenator with otherwise nonbonded circuits. A favorable clinical outcome in terms of reduced ventilatory time and hence a possibly shorter intensive care unit stay may be achievable with this device. The cost-benefit implications of using a heparin-bonded oxygenator (which is only 10% more expensive than an isolated nonbonded oxygenator) versus custom-built heparin-bonded circuitry (which is 40% to 50% more expensive than commonly used nonbonded circuits) remain to be established and addressed.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 
Address reprint requests to Mr Ashraf, Cardiothoracic Surgery Department, Leeds General Infirmary, Great George St, Leeds, UK LS1 3EX.

This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/annals

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comment References

 

1. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845–57.[Abstract]
2. Steinberg JB, Kapelanski DP, Olson JD, Weiler JM. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;106:1008–16.[Abstract]
3. Kawamura T, Wakusawa R, Okada K, Inada S. Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin-8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016–21.[Medline]
4. Finn A, Naik S, Nigel K, Levinsky RJ, Strobel S, Elliott M. Interleukin-8 release and neutrophil degranulation after paediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;105:234–41.[Abstract]
5. Kalfin RE, Engelman RM, Rousou JA, et al. Induction of interleukin-8 expression during cardiopulmonary bypass. Circulation 1993;88:401–6.
6. Hennein HA, Ebba H, Rodriguez JR, et al. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg 1994;108:626–35.[Abstract/Free Full Text]
7. Bando K, Pillai R, Cameron DE. Leukocyte depletion ameliorates free radical mediated lung injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:873–7.[Abstract]
8. Jansen NJ, van Oeveren W, van den Broek L, et al. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg 1991;102:515–25.[Abstract]
9. Gu YJ, van Oeveren W, Akkerman C, Boonstra PW, Huyzen RJ, Wildevuur CRH. Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:917–22.[Abstract/Free Full Text]
10. Videm V, Svennevig JL, Fosse E, Semb G, Osterud A, Mollnes T. Reduced complement activation with heparin-coated oxygenator and tubings in coronary bypass operation. J Thorac Cardiovasc Surg 1992;103:806–13.[Abstract]
11. Jansen PG, Velthuis H, Huybregts RA, et al. Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits. J Thorac Cardiovasc Surg 1995;110:829–34.[Abstract/Free Full Text]
12. Steinberg BM, Grossi E, Schwartz D, et al. Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann Thorac Surg 1995;60:525–9.[Abstract/Free Full Text]
13. Edmunds HL, Campbell FW. Platelet function and cardiopulmonary bypass. In: Gravlee GP, Davis RF, Utley JR, eds. Cardiopulmonary bypass: principles and practice. Baltimore: Williams & Wilkins, 1993:407–35.
14. Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552–9.[Abstract/Free Full Text]
15. Lotz M. Interleukin-6. Cancer Invest 1993;11:732–42.[Medline]
16. Damas P, Ledoux D, Nys M, et al. Cytokines serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg 1992;215:356–62.[Medline]
17. Moore FD, Warner KG, Assousa S, Valeri CR, Khuri SF. The effect of complement activation during cardiopulmonary bypass. Ann Surg 1988;208:95–103.[Medline]
18. Mollnes TE, Videm V, Riesenfeld J, et al. Complement activation and bioincompatibility: the terminal complement complex for evaluation, and surface modification with heparin for improvement of biomaterials. Clin Exp Immunol 1991;88(Suppl 1):21–6.
19. Deppisch R, Schmitt V, Bommer J, Hansch GM, Ritz E, Rautenberg EW. Fluid phase generation of terminal complement complex as a novel index of bioincompatibility. Kidney Int 1990;37:696–706.[Medline]
20. Boackle RJ, Caughman GB, Vesely J, Medgyeshi G, Fudenberg HH. Potentiation of factor H by heparin: a rate limiting mechanism for inhibition of the alternative complement pathways. Mol Immunol 1983;20:1157–64.[Medline]
21. Maillet F, Kazatchkine MD, Glotz D, Fischer E, Rowe M. Heparin prevents the formation of human C3 amplification convertase by inhibiting the binding site for B on C3b. Mol Immunol 1983;20:1401–4.[Medline]
22. Videm V, Mollnes TE, Garred P, Svennevig JL. Biocompatibility of extracorporeal circulation: in vitro comparison of heparin-coated and uncoated oxygenator circuits. J Thorac Cardiovasc Surg 1991;101:654–60.[Abstract]
23. Wachtfogel YT, Kucich U, Greenplate J, et al. Human neutrophil degranulation during extracorporeal circulation. Blood 1987;69:324–30.[Abstract/Free Full Text]
24. Bazzoni F, Cassatella MA, Rossi F, Ceska M, Dewald B, Baggiolini M. Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J Exp Med 1991;173:771–4.[Abstract/Free Full Text]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kevin G. Watterson Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ashraf, S. Articles by Watterson, K. G. Search for Related Content PubMed PubMed Citation Articles by Ashraf, S. Articles by Watterson, K. G.